This laboratory has identified 3 sarcoma-associated antigens, S1, S2 and S3, which are present in human sarcoma cells growing in tissue culture. In addition, the classical heterophile substances, Forssman and serum sickness antigens, have been shown to be associated with sarcoma and other forms of malignancy. The titers of antibody to Forssman antigen are significantly elevated in sarcoma patients and the prevalence of antibody to serum sickness antigen can be observed. Recent immunologic studies have shown that both S1 and S3 are present also in boiled guinea pig tissue and, therefore, "heterophile" in nature. They are not present in sheep red blood cells, whereas the classic heterophile antigen, Forssman, infectious mononucleosis and serum sickness. Efforts to isolate human tumor antigens have, in general, been hindered by a lack of sufficient substrate for biochemical purification. The presence of antigen capable of absorbing antibody to S1 and S3 in guinea pig kidney tissue presents an unusual opportunity for the biochemical isolation of substances sharing reactivity with human tumor antigens without concern for the quantity of tissue needed. Once purified antigens are available, radioimmunoassays can be prepared which can be used to define more precisely the distribution of antigens in human tissues and the prognostic implications of changes in antigen and antibody levels. Since multiple antigens are present in guinea pig kidney to which patients may have antibody, this study design provides for first cataloguing the distribution of such antigens in fractions prepared by extraction procedures. The antigens found will then be characterized to determine whether they represent known substances or, if new, whether there is any evidence of tumor-relatedness. Purification of S1, S3 and other relevant antigens will then be undertaken. It is anticipated that this study will provide important new insights into the nature of antigens which frequently provoke cross-reactive but yet clearly tumor-related immune responses in patients with sarcoma and other solid tumors.